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Principle figure by Ramachandraiah et al. (2014).

MICROFLUIDIC CELL SIZE SORTING INSTRUMENT PACK

Spiral channel for microfluidic inertial cell sorting by size
EASY CELL SORTING EXPERIMENT

Unbox, set up and start your experiments right away

SPIRAL CELL SORTING CHIP

Passive, inertia-based sorting of the cells by size

THE ADVANTAGES OF MICROFLUIDICS

Low reagent consumption, improved safety, easier to use

Microfluidic cell sorting

Cells can be sorted depending on their size by using the microfluidic cell size sorting pack. This pack is based on the high-accuracy OB1 flow controller (Elveflow) and a spiral sorter chip, this all-in-one solution contains all the required microfluidic instruments to set up a cell sorting system with high flow rate and good sorting performance. Our microfluidic experts will help you throughout the whole setup process of your experiment making this pack usable by microfluidic technology beginner users.

 

The cell separation technique is label-free, membrane-free and is based on well understood dean forces. This pack can also be used to separate sperm cells from red blood cells.

A microfluidic cell sorting pack contains an OB1 microfluidic flow controller to push the sample containing the cells inside the microfluidic chip that uses Dean force to separate them by size. The efficiency of the sorting will be directly linked to the fluids properties but also on the flow rate inside the channel.

 

The throughput of the process can be easily increased by parallelized the process with the use of several microfluidic channels at the same time thanks to a manifold that will separate the flow before the microfluidic chip.

 

This pack can also be used for passive sperm sorting.

 

Microfluidic cell sorting pack setup

This pack brings together different instruments that are compatible and allows you to easily start the experiment. A single software pilots everything and it can be adapted and applied to other different ends. This is why we develop packs for researchers and industries that are beginners or experts in the field of microfluidics. The following figure summarizes the montage that can be set up with the pack.

Cell sorting setup

The cell sorting pack contains:

  • OB1 flow controller (Elveflow)
  • MFS flow sensor (or BFS flow sensor) (Elveflow)
  • 15 mL Falcons
  • A commercial spiral microfluidic chip with several outlets
  • All necessary accessories: connectors, filters, tubing, etc…
  • Software for control and automation (Elveflow)

Microfluidic cell size sorting principle

Cell sorting is a critical step in many biological, biotechnological and medicine experiments [1]. It is especially useful to enrich cell samples by increasing their concentration for diagnostic or treatments [2]. It can also be used to remove cells from plasma which is necessary for some early cancer detection techniques that use serum biomarkers [3-4].

 

There are several methods to sort cells in a microfluidic chip including acoustic, magnetic and optical mechanisms [5]. The microfluidic cell size sorting Pack uses a label-free inertial separation and sorting technique using Dean forces that create vortices inside the microchannel [6]. Theses vortices appear in the spiral shape channel because of the velocity difference between the fluid near the inner wall and the velocity of the fluid near the outer wall of the microfluidic channel [7].

 

Therefore, the balance between the Dean force and the inertial force creates a separation between the smaller cells that are dragged toward the outlet of the spiral because the Dean force is predominant and the larger cells are dragged toward the inner wall of the microchannel [8].

The effectiveness of the sorting depends on the Dean Number. This number increases when the Reynolds number increases and the radius of curvature decreases [9].

References
  1. C. Wyatt Shields IV, Catherine D. Reyes and Gabriel P. López, Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation. Lab Chip, 2015, 15, 1230-1249
  2. Gossett, D.R., Weaver, W.M., Mach, A.J. et al. Label-free cell separation and sorting in microfluidic systems. Anal Bioanal Chem 397, 3249–3267 (2010)
  3. Villanueva J., Shaffer D., Philip J., Chaparro C., Erdjument-Bromage H., Olshen A., Fleisher M., Lilja H., Brogi E., Boyd J., Sanchez-Carbayo M., Holland E., Cordon-Cardo C., Scher H., Tempst P., Differential exoprotease activities confer tumor-specific serum peptidome patterns, J. Clin. Invest., 116, 271–284 (2006)
  4. Jinong Li, Zhen Zhang, Jason Rosenzweig, Young Y Wang, Daniel W Chan, Proteomics and Bioinformatics Approaches for Identification of Serum Biomarkers to Detect Breast Cancer, Clinical Chemistry, 48, 8, 1 August 2002, 1296–1304
  5. Pu Chen, Xiaojun Feng, Wei Du, Bi-Feng Liu, Microfluidic chips for cell sorting, Frontiers in Bioscience 13, 2464-2483, January 1, 2008
  6. Nivedita, N., Ligrani, P. & Papautsky, I. Dean Flow Dynamics in Low-Aspect Ratio Spiral Microchannels. Sci Rep 7, 44072 (2017).
  7. Zhang J., Yan S., Yuan D., Alici G., Nguyen N-T., Warkiani M.E., Li W., Fundamentals and applications of inertial microfluidics: a review, Lab Chip, 2016, 16, 10-34
  8. Al-Faqheri, W., Thio, T.H.G., Qasaimeh, M.A. et al. Particle/cell separation on microfluidic platforms based on centrifugation effect: a review. Microfluid Nanofluid 21, 102 (2017).
  9. Yoon DH, Ha JB, Bahk YK, et al. Size-selective separation of micro beads by utilizing secondary flow in a curved rectangular microchannel. Lab on a Chip. 2009 Jan;9(1):87-90.

Why use microfluidics for cell size sorting?

The basic principle of microfluidics is to use tiny volumes of sample which can be a critical improvement for valuable cell solutions.

Moreover, cell sorting on microchips are simpler than more conventional methods as it is label-free and relies only on mechanical forces and, moreover, eliminates potential biohazardous aerosols.

Cell sorting using a spiral microchannel relies on the Dean forces which are stronger when the Reynolds number is low. The Reynolds number in a microfluidic channel is usually very low therefore this cell sorting technique is almost only usable in microfluidics experiment conditions.

 

It is possible to optimize cell sorting by tuning the fluid velocity. there is also the possibility to use up to different outlets on one microfluidic chip to separate different entities.

To summarize, microfluidic spiral chips allow more flexible, precise and efficient cell sorting.

Cell sorting can be integrated in bigger microfluidic platforms for more complex processes.

Cell-sorting-Pack Dean
Particle/cell migration in straight and curved channel (a) in straight channel, shear gradient lift force (FLS) push particles toward the channel walls, and wall induced lift force (FLW) that repulses them back toward the center line of the channel (b) in spiral channel, the balance between net inertial lift force (FL) and Dean drag force (FD) causes particle migration to equilibrium position [1].

1. Al-Faqheri, W., Thio, T.H.G., Qasaimeh, M.A. et al. Particle/cell separation on microfluidic platforms based on centrifugation effect: a review. Microfluid Nanofluid 21, 102 (2017).

Customize your cell sorting pack

It is possible to find commercially available spiral chips for cell sorting with different materials, spiral and channel sizes. You can also fabricate your own design various fabrication technics.

The efficiency of the sorting depends on the Reynolds and the Dean numbers. If some doubts remain about the settings that are best suited for a specific application, get in touch with one of our experts!

 

Supplementary Flow controller channels and flow rate sensors can be added to the Pack to fit a specific application.
Bubble can be a problem when mixing, a bubble remover can be provided to tackle this issue if it is critical for the experiment.

 

Contact our experts to answer any questions about this cell sorting Pack and how it can match your specifications by sending a message via the button below.

– Check our other Packs for various applications –

How can we help your experiment?

The packs applications are still under development, so we are not able to give you the tips or troubleshooting advice that we usually give in our user guides and application notes for the possible challenges you could face for a specific application experiment. That being said, we can always guarantee reliable and high-precision microfluidic flow control. Our microfluidic instruments are high-performance, versatile and user-friendly. Our experts will bring support and expertise during the setup and implementation of this sensor calibration pack.

Yes! Our experts will establish which instruments are best suited for your application, such as the type of flow sensor or the number of flow controller channels you need to perform your experiment. Send us a message: 

innovation@microfluidic.fr

You can order our instruments on the product section of our website.

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